Importantly, genetic evidence reveals a clear involvement of UPS dysfunction in PD pathogenesis: familial PD-associated genetic variations have been identified on PARK2 (Kitada et al., 1998) and UCHL1 (Leroy et al., 1998; Maraganore et al., 1999), which encode the ubiquitin E3 ligase parkin and deubiquitinating enzyme UCHL1, respectively. The gene discussed is PRKN; the disease is Parkinson disease.